English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background    MET  proto-oncogene amplification (amp) is an important mechanism underlying acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the optimal treatment strategy after acquiring  MET- amp-mediated EGFR-TKI resistance remains controversial. Our study compared three treatment strategies for patients with  EGFR -mutant non-small-cell lung cancer (NSCLC) who were detected with  MET- amp at EGFR-TKI progression using next-generation sequencing.    Methods  Of the 70 patients included in the study, 38 received EGFR-TKI + crizotinib, 10 received crizotinib monotherapy, and 22 received chemotherapy. Clinical outcomes and molecular profiles were analyzed.    Results  The objective response rate was 48.6% for EGFR-TKI + crizotinib group, 40.0% for crizotinib monotherapy group, and 18.2% for chemotherapy group. Patients who received EGFR-TKI + crizotinib had significantly longer progression-free survival than those who received crizotinib or chemotherapy (5.0  vs . 2.3  vs . 2.9 months, p = 0.010), but overall survival was comparable (10.0  vs . 4.1  vs . 8.5 months, p = 0.088).  TP53  mutation (58.5%) and  EGFR- amp (42.9%) were frequent concurrent mutations of the cohort. Progression-free survival was significantly longer for patients with either concurrent  TP53  mutation (n = 17) (6.0  vs . 2.3  vs . 2.9 months, p = 0.009) or  EGFR- amp (n = 13) (5.0  vs . 1.2  vs . 2.4 months, p = 0.016) in the EGFR-TKI + crizotinib group than the other two regimen. Potential acquired resistance mechanisms to EGFR-TKI + crizotinib included  EGFR -T790M (n = 2),  EGFR- L718Q (n = 1),  EGFR -S645C (n = 1),  MET -D1228H (n = 1),  BRAF -V600E (n = 1),  NRAS -Q61H (n = 1),  KRAS- amp (n = 1),  ERBB2- amp (n = 1),  CDK4- amp (n = 1), and  MYC- amp (n = 1).    Conclusion  Our study provides real-world clinical evidence from a large cohort that simultaneous inhibition of  EGFR  and  MET  could be a more effective therapeutic strategy for patients with  MET- amp acquired from EGFR-TKI therapy.

frontiers in oncology

A Large Real-World Study on the Effectiveness of the Combined Inhibition of EGFR and MET in EGFR-Mutant Non-Small-Cell Lung Cancer After Development of EGFR-TKI Resistance